Genetic Variant BPIFC:c.531-27_531-16dupTTTTTTTTTTTT (chr22-32445713-G-GAAAAAAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_174932.3(BPIFC):c.531-27_531-16dupTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0040 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0042 ( 19 hom. )

Failed GnomAD Quality Control

Consequence

BPIFC
NM_174932.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

Publications

0 publications found

Variant links:

Genes affected

BPIFC (HGNC:16503): (BPI fold containing family C) Predicted to enable lipid binding activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

BPIFC Gene-Disease associations (from GenCC):

trichilemmal cyst
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BPIFC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174932.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFC	NM_174932.3	MANE Select	c.531-27_531-16dupTTTTTTTTTTTT		intron	N/A	NP_777592.1	Q8NFQ6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BPIFC	ENST00000300399.9	TSL:1 MANE Select	c.531-16_531-15insTTTTTTTTTTTT	intron	N/A	ENSP00000300399.3	Q8NFQ6-1
BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insTTTTTTTTTTTT	intron	N/A	ENSP00000380594.1	Q8NFQ6-1
BPIFC	ENST00000534972.4	TSL:5	n.236-16_236-15insTTTTTTTTTTTT	intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes

AF:

0.00401

AC:

305

AN:

75966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00376

Gnomad AMI

AF:

0.00865

Gnomad AMR

AF:

0.00362

Gnomad ASJ

AF:

0.00261

Gnomad EAS

AF:

0.00549

Gnomad SAS

AF:

0.00129

Gnomad FIN

AF:

0.00145

Gnomad MID

AF:

0.0263

Gnomad NFE

AF:

0.00421

Gnomad OTH

AF:

0.00508

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00417

AC:

2636

AN:

631884

Hom.:

Cov.:

AF XY:

0.00476

AC XY:

1520

AN XY:

319200

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00355

AC:

AN:

16346

American (AMR)

AF:

0.00870

AC:

126

AN:

14484

Ashkenazi Jewish (ASJ)

AF:

0.00483

AC:

AN:

11586

East Asian (EAS)

AF:

0.00519

AC:

123

AN:

23706

South Asian (SAS)

AF:

0.0131

AC:

507

AN:

38810

European-Finnish (FIN)

AF:

0.00489

AC:

109

AN:

22300

Middle Eastern (MID)

AF:

0.00613

AC:

AN:

1958

European-Non Finnish (NFE)

AF:

0.00324

AC:

1540

AN:

474762

Other (OTH)

AF:

0.00376

AC:

105

AN:

27932

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.391

Heterozygous variant carriers

122

244

365

487

609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00401

AC:

305

AN:

75978

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

145

AN XY:

33368

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00375

AC:

AN:

20518

American (AMR)

AF:

0.00361

AC:

AN:

4982

Ashkenazi Jewish (ASJ)

AF:

0.00261

AC:

AN:

2298

East Asian (EAS)

AF:

0.00550

AC:

AN:

2000

South Asian (SAS)

AF:

0.00130

AC:

AN:

1542

European-Finnish (FIN)

AF:

0.00145

AC:

AN:

692

Middle Eastern (MID)

AF:

0.0263

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00421

AC:

178

AN:

42306

Other (OTH)

AF:

0.00507

AC:

AN:

986

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.394

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.098

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

22-32445713-GAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over